Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Guangdong Landau Biotechnology Co. Ltd., Guangzhou, China.
J Neurotrauma. 2020 Aug 1;37(15):1669-1686. doi: 10.1089/neu.2019.6822. Epub 2020 May 4.
Non-human primate (NHP) spinal cord injury (SCI) models can be informative in the evaluation of treatments that show promise in rodent models prior to translation to humans. In the present study, we aimed to establish a cervical spinal hemi-contusion model with controlled displacement and evaluate the abnormalities in behavior, electrophysiology, histology, and magnetic resonance imaging. Twelve adult NHPs were divided into an SCI group ( = 8, 24 and 48 weeks) and a control group ( = 4). An impactor (Φ = 4 mm) was driven to compress the left C5 cord at 800 mm/sec. The contusion displacement and peak force was 4.08 ± 0.17 mm and 19.8 ± 4.6 N. The behavioral assessment showed a consistent dysfunction below the wrist and spontaneous recovery of limb function after injury. Lesion length and lesion area at the epicenter based on T2 hyperintensity were 5.68 ± 0.47 mm and 5.99 ± 0.24 mm at 24 weeks post-injury (wpi), and 5.29 ± 0.17 mm and 5.95 ± 0.24 mm at 48 wpi. The spared spinal cord area immuno-positive for glial fibrillary acidic protein was significantly reduced, while the staining intensity increased at 24 wpi and 48 wpi, compared with the sham group. Ipsilateral somatosensory and motor evoked potentials were dynamic, increasing in latency and decreasing in amplitude compared with pre-operative values or the contralateral values, and correlated to varying degrees with behavioral outcomes. A shift in size-frequency distribution of sensory neurons of the dorsal root ganglia (DRG) was consistent with a loss of large-diameter cells. The present study demonstrated that the NHP SCI model resulted in consistent unilateral limb dysfunction and potential plasticity in the face of loss of spinal cord and DRG tissue.
非人类灵长类动物(NHP)脊髓损伤(SCI)模型在评价在向人类转化之前在啮齿动物模型中显示出前景的治疗方法方面具有信息价值。在本研究中,我们旨在建立一种具有受控位移的颈椎半挫伤模型,并评估行为、电生理学、组织学和磁共振成像的异常。12 只成年 NHP 分为 SCI 组(=8、24 和 48 周)和对照组(=4)。冲击器(Φ=4mm)以 800mm/sec 的速度驱动压缩左侧 C5 脊髓。挫伤位移和峰值力为 4.08±0.17mm 和 19.8±4.6N。行为评估显示手腕以下功能持续障碍,肢体功能在损伤后自发恢复。基于 T2 高信号的损伤长度和损伤中心面积在损伤后 24 周(wpi)分别为 5.68±0.47mm 和 5.99±0.24mm,在 48 wpi 分别为 5.29±0.17mm 和 5.95±0.24mm。胶质纤维酸性蛋白免疫阳性的脊髓残存面积明显减少,而在 24wpi 和 48wpi 时,染色强度增加,与假手术组相比。同侧体感和运动诱发电位的潜伏期延长,幅度降低,与术前值或对侧值相比,与行为结果呈不同程度相关。背根神经节(DRG)感觉神经元的大小-频率分布的变化与大直径细胞的丧失一致。本研究表明,NHP SCI 模型导致一致的单侧肢体功能障碍,并在脊髓和 DRG 组织丧失的情况下具有潜在的可塑性。